Tumor antigen-specific CD4+ helper T cells play critical roles in the induction and maintenance of anti-tumor immune responses by providing “CD4-help”. Activation of CD4+ T cells at the local tumor sites is believed to help overcome multiple immuno-suppression mechanisms and promote tumor eradication by the immune system. However, because of the frequent lack of functional antigen-presenting cells at the local tumor sites, activation of the CD4+ T cells and therefore the provision of CD4-help at the local tumor site is severely limited. There is accordingly an ongoing and unmet need to provide new compositions and methods such that activation of CD4+ T cells and therefore provision of CD4-help can be achieved.